Interactions of the cellular nuclear proteins with the HIV-1 long terminal repeat (LTR) play a central role in the regulation of viral gene expression, and therefore in HIV-1 latency and activation. These proteins include constitutively expressed host transcription factors, as well as repressors and inducible activators of gene activity. We have identified several distinct partial cDNA clones coding for proteins that bind to a probe consisting of multimers of a sequence that span a negative regulatory element in the LTR. Our plan is to isolate full-length cDNA molecules corresponding to the partial cDNA clones in order to examine the structure, DNA binding properties, and biological activities of the encoded proteins. Since there are certain regions in the LTR that have not been shown to contain protein binding sites, it is necessary to explore other T-cell activation procedures in order to investigate the protein binding properties of these regions. Once novel protein binding sites are established, it would become possible to make use of appropriately prepared T-cell expression libraries to directly identify cDNA clones corresponding to these proteins so that their functions in regulation of HIV gene expression can be examined.